Performance of drug resistance assays in testing HIV-1 non-B subtypes

Antiretroviral susceptibility analyses were performed in plasma samples collected from 32 HIV-1 non-B-infected individuals, most of whom had received antiretroviral drugs. Reverse transcriptase (RT) and protease gene sequences were obtained, and 15 anti-HIV drugs were tested in a recombinant virus phenotypic assay. Phenotypic results were obtained in 25 (78.1%) samples, while genotypic data were recorded in 19 (59.4%). In seven samples (21.9%), neither genotypic nor phenotypic results were obtained. Ten of 13 samples with plasma HIV RNA below 2000 copies/mL did not yield genotypic results. Resistance assays work accurately when testing HIV-1 non-B subtypes. However, as for subtype B variants, a low viral load is the most important factor limiting the application of these tests

The effect of partial depopulation on Campylobacter introduction in broiler houses

Poultry is seen as the main reservoir for Campylobacter. Control of this zoonotic pathogen in primary production could potentially reduce the colonization in broiler flocks and consequently reduce the number of human infections. In the present study, 20 broiler flocks from 10 farms, were sampled immediately before and 5 to 7 d after partial depopulation (thinning) for the presence of Campylobacter using cecal droppings and overshoes. At the time of thinning, the catching crew, transportation vehicles, forklift, and transport containers were sampled for the presence of Campylobacter. Samples were cultivated; presumed positive isolates were confirmed by PCR. The isolates were molecularly typed by flaA restriction analysis and pulsed field gel electrophoresis. Results show that all flocks were thinned using Campylobacter-contaminated equipment and materials. One-third of the broiler flocks became colonized after thinning. In 67% of the colonization cases, identical strains were found matching those of container systems, transport trucks, and/or forklifts. This identifies thinning as an important risk factor for Campylobacter introduction into broiler houses. Setup and compliance with biosecurity practices during thinning is essential to prevent Campylobacter colonization of broiler flocks

A field induced ferromagnetic-like transition below 2.8 K in Li2CuO2: An experimental and theoretical study

The low temperature magnetic properties of the Li2CuO2 compound have been investigated by means of superconducting quantum interference device magnetometry. We find in addition to an antiferromagnetic phase below 9.5 K a ferromagnetic-like steep rise of the magnetization around 2.8 K. The observed low temperature behavior is discussed by considering second and fourth order magnetocrystalline effective anisotropy coefficients, in addition to the exchange couplings reported in the literature.Work at the Institut de Ciencia dels Materials was supported by the Spanish Comisión Interministerial de Ciencia y Technología Grant No. CICYT MAT 96-1037

Cross-validated stepwise regression for identification of novel non-nucleoside reverse transcriptase inhibitor resistance associated mutations

<p>Abstract</p> <p>Background</p> <p>Linear regression models are used to quantitatively predict drug resistance, the phenotype, from the HIV-1 viral genotype. As new antiretroviral drugs become available, new resistance pathways emerge and the number of resistance associated mutations continues to increase. To accurately identify which drug options are left, the main goal of the modeling has been to maximize predictivity and not interpretability. However, we originally selected linear regression as the preferred method for its transparency as opposed to other techniques such as neural networks. Here, we apply a method to lower the complexity of these phenotype prediction models using a 3-fold cross-validated selection of mutations.</p> <p>Results</p> <p>Compared to standard stepwise regression we were able to reduce the number of mutations in the reverse transcriptase (RT) inhibitor models as well as the number of interaction terms accounting for synergistic and antagonistic effects. This reduction in complexity was most significant for the non-nucleoside reverse transcriptase inhibitor (NNRTI) models, while maintaining prediction accuracy and retaining virtually all known resistance associated mutations as first order terms in the models. Furthermore, for etravirine (ETR) a better performance was seen on two years of unseen data. By analyzing the phenotype prediction models we identified a list of forty novel NNRTI mutations, putatively associated with resistance. The resistance association of novel variants at known NNRTI resistance positions: 100, 101, 181, 190, 221 and of mutations at positions not previously linked with NNRTI resistance: 102, 139, 219, 241, 376 and 382 was confirmed by phenotyping site-directed mutants.</p> <p>Conclusions</p> <p>We successfully identified and validated novel NNRTI resistance associated mutations by developing parsimonious resistance prediction models in which repeated cross-validation within the stepwise regression was applied. Our model selection technique is computationally feasible for large data sets and provides an approach to the continued identification of resistance-causing mutations.</p

The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors

The human immunodeficiency virus type 1 (HIV-1) protease mutation D30N is exclusively selected by the protease inhibitor (PI) nelfinavir and confers resistance to this drug. We demonstrate that D30N increases the susceptibility to saquinavir (SQV) and amprenavir in HIV-1 subtype B isolates and that the N88D mutation in a D30N background neutralizes this effect. D30N also suppresses indinavir (IDV) resistance caused by the M46I mutation. Interestingly, in patients with viruses originally containing the D30N mutation who were treated with IDV or SQV, the virus either reversed this mutation or acquired N88D, suggesting an antagonistic effect of D30N upon exposure to these PIs. These findings can improve direct salvage drug treatment in resource limited countries where subtype B is epidemiologically important and extend the value of first and second line PIs in these populations

Hepatitis B virus : specific binding and internalization of small HBsAg by human hepatocytes

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